Squamous cell carcinoma

We don’t often think of skin cancers as a secondary to lymphedema. But, the reality is that due to the malfunction lymph system our limbs that are affected by lymphedema are immunocompromised.

In addition to being immunicompromised, the skin is often very damaged by lymphedema and the complications associated with it. The skin is usually thick and fibrotic plus it may have weeping areas, papulosis, a “cobblestone” appearance and impaired vascular flow.

Unfortunately, this places us in the higher then average risk level for skin cancers, lymphatic cancers and other malignant skin tumors or growths.

While squamous cell carcinoma is the second leading skin cancer, if caught
Early can be thrown into complete remission. Therefore, it is extremely important for us to learn about it and in how to recognize it.

Squamous cell carcinoma arising from chronic Lymphedema has only been reported in the literature 11 times (12 cases). Some aspects of its pathogenesis remain unclear and, for the first time, attention has been drawn to epidemiological data.

CASE REPORT:

A 90-year-old white female with chronic unilateral lower-limb lymphedema, secondary to trauma 20 years earlier, presented with a three-month history of a vegetating cutaneous lesion. There had not been any previous local ulceration. The tumor was completely excised and the histopathological analysis showed that it was an infiltrating squamous cell carcinoma. A literature review in the Medline (Medical Literature Analysis and Retrieval System Online) and Lilacs (Literatura Latino-Americana e do Caribe em Ciências da Saúde) databases using the MeSH (Medical Subject Heading) terms “Carcinoma, Squamous Cell” AND “Lymphedema” identified 112 references and found 12 similar case reports.

INTRODUCTION

Despite the known propensity of areas of congenital or acquired chronic lymphedema to develop malignancy, there are few reports in the literature correlating this with squamous cell carcinoma. Our review found only 11 such reports (12 cases, Table 1).1-10 There has been little discussion and emphasis on the epidemiological characteristics and carcinogenetic predisposition of chronic lymphadema.1-3 Tumor development in areas of chronic lymphedema is believed not to happen serendipitously,1,2 and inherited susceptibility to carcinogenic stimuli4,5 is thought to play a role. Knowledge about predisposing dermatological conditions and epidemiological features is very important, in order to diagnose the disease at an early stage.

CASE REPORT

A 90-year-old white female with chronic unilateral lower-limb lymphedema, secondary to trauma 20 years earlier, presented with a three-month history of a vegetating cutaneous lesion measuring 1.5 x 1.2 cm, on the anteromedial face of her right leg. There had not been any previous local ulceration. Physical examination did not show any lymph node enlargement in the groin on the same side. Abdominal ultrasound and chest radiography did not show any organ involvement. The tumor was completely excised with one-centimeter surgical margins, and the wound was closed. Histopathological analysis on the biopsy specimen showed an infiltrating squamous cell carcinoma, with free surgical margins. A follow-up 20 months later showed controlled local disease.

DISCUSSION

A review of the literature in the Medline (Medical Literature Analysis and Retrieval System Online) and Lilacs (Literatura Latino-Americana e do Caribe em Ciências da Saúde) databases using the MeSH (Medical Subject Heading) terms “Carcinoma, Squamous Cell” AND “Lymphedema” identified and found 11 similar case reports with 12 cases (Table 1).

Lymphedema may be primary or secondary to either disease or surgery. Primary lymphedema is sometimes congenital (Milroy's disease), but it may also develop at any time of life, particularly during puberty. According to the literature search results, the etiology of squamous cell carcinoma associated with chronic lymphedema was congenital in three reported cases and secondary to acquired conditions in the others. In the review of the literature, acquired chronic lymphedema was classified according to its pathophysiological mechanism, as follows: post-lymphadenectomy in three instances, idiopathic in two, secondary to trauma in three and lymphedematous in one, as well as in the present case report. 67% of the cases were located in the lower limbs and 33% in the upper limbs (Table 1). In fact, secondary postsurgical lymphedema of the extremities is the most common form in developed countries.4-6
Eight patients (67%) were diagnosed during their active middle age. The time lapse from lymphedema to tumor diagnosis was not established in the case reports. In addition, the limited number of cases does not allow conclusions to be reached regarding the relationship between the duration of chronic lymphedema and the development of squamous cell carcinoma. A speculative but noteworthy trend towards late onset was seen among the patients with congenital etiology (37, 53 and 63 years). Conversely, the time taken for squamous cell carcinoma to develop in cases of acquired chronic lymphedema may range from a few years to decades. Slightly greater female incidence (59%) of squamous cell carcinoma and chronic lymphedema was noticed. Post-mastectomy lymphedema in two patients probably accounted for this difference.2,5

Although rarely found in areas of chronic lymphedema, squamous cell carcinoma is frequently related to chronic cicatricial areas, especially those due to burns (Marjolin's ulcer). Among the additional dermatological risk factors (seen in 50% of the cases) for the development of squamous cell carcinoma are angiosarcoma, vulgar wart, chronic verrucous hyperplasia, wart-like epidermodysplasia, generalized vitiligo, dystrophic bullous epidermolysis and ultraviolet B (UVB) therapy (Table 1). Like in other cases reported in the literature,1-3,6,8 no other additional factor was noticed in our case. Some theories attempting to explain a putative mechanism have been put forward. Futrell and Myers highlighted the immunological status governing the response of animal hosts to skin-implanted tumors, with or without an intact lymphatic system. It was noticed, in their study, that although the tumoral solution failed to induce malignancy when injected into an area where the lymphatic vessels had been spared, large and lethal tumors developed whenever the injection was in an area where the lymphatics had been impaired.11

It is also believed that deficiencies in the lymphatic drainage system hamper early recognition of tumor-specific antigens.1 Chronic stasis, thereby producing local changes in the lymphatic protein composition (decreased alpha-2 globulin fraction and increased albumin-globulin ratio) and delaying protein transportation from the interstitial space into the lymphatic tissue, might change the tissue antigenic composition and/or regional immunological competence.4-6

The treatment of choice is complete surgical resection of the tumor with free margins, associated with ipsilateral lymphadenectomy in cases of lymph node metastasis. Radiation therapy and chemotherapy are used as adjunctive approaches.4,6,12 This calls for periodic follow-up of predisposed subjects, with the aim of early diagnosis and adequate surgical management.

Every patient suffering from chronic lymphedema needs to be educated about the importance of good hygiene, regular follow-up, and elevation and elastic compression of the affected limb.

RESULTS: The tumor was treated by wide excision and covered by a skin graft.

CONCLUSION: In most of the other reported SCC cases in lymphedema, there are additional factors for carcinogenesis. There is no additional carcinogenic factor except for chronic lymphedema in our case. This strongly supports that lymphedema itself is one of the carcinogenic factors for not only angiosarcoma but also SCC.

Squamous carcinoma of the foot arising in association with long-standing verrucous hyperplasia in a patient with congenital lymphedema

Cancer. 1984 Sep

Epstein JI, Mendelsohn G.

Abstract

A patient is reported with congenital lymphedema who developed a squamous cell carcinoma on his affected foot. Parallels are drawn between the development of a squamous cell carcinoma with condylomatous and spindle cell features arising in a setting of long-standing verrucous hyperplasia, as seen in this patient, and the well-recognized phenomenon of angiosarcoma occurring in areas of lymphangiomatous proliferation in patients with chronic lymphedema. The importance of a random genetic mutation occurring in hyperplastic tissue in an immunologically privileged site is discussed. Additional consideration is given, in the current case, to the possibility of viral oncogenesis and the role of ulceration as a promoter factor.

Squamous cell skin cancer

has been injured or inflamed. Most skin cancers occur on skin that is regularly exposed to sunlight or other ultraviolet radiation. Skin cancer is most often seen in people over age 50.

Squamous cell carcinoma in situ (also called Bowen's disease) is the earliest form of squamous cell cancer. The cancer has not yet invaded surrounding tissue. It appears as large reddish patches (often larger than 1 inch) that are scaly and crusted.

Actinic keratosis is a precancerous skin lesion. In rare cases it may become a squamous cell cancer.
Risks for squamous cell skin cancer include:

• Having light-colored skin, blue or green eyes, or blond or red hair
• Long-term, daily sun exposure (such as in people who work outside)
• Many severe sunburns early in life
• Older age
• A large number of x-rays
• Arsenic
• Chemical exposure

Squamous cell cancer spreads faster than basal cell cancer, but still may be relatively slow-growing. Rarely, it can spread (metastasize) to other locations, including internal organs.

Symptoms:

The main symptom of squamous cell skin cancer is a growing bump that may have a rough, scaly surface and flat reddish patches.

The bump is usually located on the face, ears, neck, hands, or arms, but may occur on other areas.

A sore that does not heal can be a sign of squamous cell cancer. Any change in an existing wart, mole, or other skin lesion could be a sign of skin cancer.

Exams and tests:

Your doctor will check your skin and look at the size, shape, color, and texture of any suspicious areas.
If skin cancer is a possibility, a piece of skin will be removed from the area and examined under a microscope. This is called a skin biopsy. A biopsy must be done to confirm the diagnosis of basal cell carcinoma or other skin cancers.
There are many types of skin biopsies. The exact procedure depends on the location of the suspected skin cancer.

Skin cancer has a high cure rate if it is treated early. Treatment depends on how big the tumor is, its location, and how far it has spread (metastasis).

• Excision refers to cutting out the tumor and using stitches to place the skin back together.

• Curettage and electrodesiccation scrapes away the cancer and uses electricity to kill any remaining cancer cells. It is used to treat cancers that are not very large or deep.

• Mohs surgery involves cutting out a layer of the skin cancer and immediately looking at it under a microscope to check if any cancer has been left behind. More layers are removed until the skin sample is free of cancer. Mohs surgery is more likely to be used for skin cancers on the nose, ears, and other areas of the face.

• Cryosurgery freezes and kills the cancer cells.

• Radiation may be used if the cancer has spread to organs or lymph nodes, or for squamous cell cancers that cannot be treated with surgery.

• Skin creams and the medications imiquimod or 5-fluorouracil may be used to treat actinic keratosis and superficial (not very deep) squamous cell carcinoma.

• Photodynamic therapy, a special type of light treatment, may be used to treat Bowen's disease (BD).
Outlook or Prognosis:

Most (95%) of squamous cell tumors can be cured if they are removed promptly. New tumors may develop, however. If you have had squamous cell cancer, have your skin regularly examined by your health care provider.

The outlook depends on a number of factors, including the type of cancer and how quickly it was diagnosed. Squamous cell carcinoma only rarely spreads to other parts of the body.

Some squamous cell skin cancers may be more difficult to treat or can spread. This risk may depend on:

• The size or shape of the cancer
• What the cancer appears like when biopsy results are examined under a microscope
• Where the skin cancer is located
• Your other health problems

Possible Complications:

• Local spread of the tumor
• Spread to other locations, including the internal organs
*Possible lymphedema from nodal removal involving biopsies, and treatments.

When to contact a Medical Professional:

Call for an appointment with your health care provider if you see the sore change in:

• Appearance
• Color
• Size
• Texture

Also call if you have pain, inflammation, bleeding, or itching of an existing skin lesion.

Prevention:

Reduce your sun exposure. Protect your skin from the sun by wearing hats, long-sleeved shirts, long skirts, or pants.
Sunlight is most intense between 10 a.m. and 4 p.m., so try to limit exposure during these hours.

Use high-quality sunscreens, preferably with sun protection factor (SPF) ratings of at least 30 that protect against both UVA and UVB sunlight. Apply the sunscreen at least 30 minutes before going outside and reapply frequently. Use a sunscreen throughout the year, even during the winter. Use a waterproof formula.

Squamous Cell Carcinoma of the Skin

Localized squamous cell carcinoma of the skin is a highly curable disease.[1] The traditional methods of treatment involve the use of cryosurgery, radiation therapy, electrodesiccation and curettage, and simple excision. Each of these methods may be useful in specific clinical situations.

Of all treatment methods available, Mohs micrographic surgery has the highest 5-year cure rate for both primary and recurrent tumors. This method uses microscopic control to evaluate the extent of tumor invasion. Lymphadenectomy is indicated when regional lymph nodes are involved.

Treatment options:

1. Mohs micrographic surgery.[2] Although this method is complicated and requires special training, it has the highest cure rate of all surgical treatments because the tumor is microscopically delineated until it is completely removed. It is indicated for the treatment of:

• primary squamous cell carcinomas when they occur at sites known to have a high initial treatment failure rate following traditional methods;
• primary tumors with poorly defined clinical borders, primary tumors with diameters more than 2 cm; or
• primary tumors arising in regions where the maximum preservation of uninvolved tissue is desirable such as the face, head, and genitalia.

Mohs micrographic surgery should be used for squamous cell carcinomas that show perineural invasion since tumor transit along nerves may extend many centimeters away from the primary or recurrent tumor site.[3] Recurrent squamous cell carcinomas can also be treated with this technique.

2. Simple excision with frozen or permanent sectioning for margin evaluation. This traditional surgical treatment usually relies on surgical margins ranging from 3 mm to 10 mm, depending on the diameter of the original tumor.[4] Tumor recurrence is not uncommon because only a small fraction of the total tumor margin is examined pathologically.

3. Electrodesiccation and curettage. This is a quick method for destroying the tumor, but the adequacy of treatment cannot be assessed immediately since the surgeon cannot visually detect the depth of microscopic tumor invasion. It should be reserved for very small primary tumors since this disease has metastatic potential.

4. Cryosurgery. Cryosurgery is used for patients with clinically well-defined in situ tumors. It is especially useful for debilitated patients with medical conditions that preclude other types of surgery.

5. Absolute contraindications for cryosurgery include abnormal cold tolerance, cryoglobulinemia, cryofibrinogenemia, Raynaud disease, and platelet deficiency disorders. Relative contraindications to cryosurgery include tumors of the scalp, ala nasi, nasolabial fold, tragus, postauricular sulcus, free eyelid margin, upper lip vermillion border, and lower legs. Caution should also be used before treating nodular ulcerative neoplasia more than 3 cm, carcinomas fixed to the underlying bone or cartilage, tumors situated on the lateral margins of the fingers and at the ulnar fossa of the elbow, or recurrent carcinomas following surgical excision. Significant morbidity is associated with the use of cryosurgery.

Edema is common following treatment, especially around the periorbital region, temple, and forehead. Treated tumors usually exude necrotic material after which an eschar forms and persists for about 4 weeks. Permanent pigment loss at the treatment site is unavoidable. Atrophy and hypertrophic scarring have been reported as well as instances of motor and sensory neuropathy.

6. Radiation therapy.

Radiation therapy is a logical treatment choice, particularly for patients with primary lesions requiring difficult or extensive surgery (e.g., eyelids, nose, or ears).[5] Radiaiton therapy eliminates the need for skin grafting when surgery would result in an extensive defect. Cosmetic results are generally good to excellent with a small amount of hypopigmentation or telangiectasia in the treatment port. Radiation therapy can also be utilized for lesions that recur after a primary surgical approach.[6]

Radiation therapy is contraindicated for patients with xeroderma pigmentosum, epidermodysplasia verruciformis, or the basal cell nevus syndrome because it may induce more tumors in the treatment area.

7. Topical fluorouracil (5-FU). This method may be helpful in the management of selected in situsquamous cell carcinomas (Bowen disease). Careful and prolonged follow-up is required since deep follicular portions of the tumor may escape treatment and result in future tumor recurrence.[7]

8. Carbon dioxide laser. This method may be helpful in the management of selected squamous cell carcinoma in situ. It may be considered when a bleeding diathesis is present, since bleeding is unusual when this laser is used.

9. Interferon alpha. Clinical trials are ongoing to treat squamous cell carcinoma with intralesional interferon alpha.[8] The results should be available in several years. One report shows the combination of interferon alpha and retinoids is effective treatment for squamous cell carcinoma.[9]

Follow-up:

• Since squamous cell carcinomas have definite metastatic potential, patients should be re-examined every 3 months for the first several years and then followed indefinitely at 6-month intervals.

Current Clinical Trials:

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with squamous cell carcinoma of the skin. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.